Myelin is metabolically very stable compared to most membranes, even in vitro intact myelin is resistant to enzymatic digestion. It is proposed that the destruction of myelin following spinal cord trauma may be initiated by the liberation or activation of endogenous hydrolases which disrupt the structure and make it susceptible to further degradation by enzymes from surrounding tissue or circulating phagocytic cells. The relatively high concentration and slow metabolic turnover of the sphingolipids in myelin has prompted several investigators to speculate that these compounds might serve as a structural core or nucleus around which the remainder of the myelin lipid is assembled. If this hypothesis is correct, it follows that metabolic degradation of the sphingolipids plays a major role in the dissolution of myelin, and the sphingolipases are likely to mediate myelin destruction. Some of the enzymes which degrade the sphingolipids have been identified and partially characterized, but their levels in various regions of the CNS or how they might be activated following trauma or disease is not known. One important reason for our lack of knowledge in this area is that it is difficult to apply the currently available assay techniques to such a study. A part of the present proposal is to develop sensitive and specific techniques for assaying the sphingolipids and the sphingolipid cleaving enzymes. Using these procedures, tissue from spinal cord-injured animals will be studied to attempt to determine the factors which regulate and control the autodestructive process which is the result of severe spinal cord injury.